CN101006337A - Sensor chip and production method therefor - Google Patents

Abstract

A sensor chip is provided. The sensor chip is provided with the board, the cover layer, the spacer layer sandwiched between the board and the cover layer, the hollow reacting part between the board and the cover layer, and a detecting means in the hollow reacting part. The board and the cover layer are made of the same material and have the same thickness. The material and the shape of the spacer layer are symmetric to a flat plane which is parallel to the board at equal distances from the board and the cover layer. The sensor chip does not warp due to changes of temperature and humidity in the environment. A method for manufacturing such sensor chip is also provided.

Description

Sensor chip and manufacturing method thereof

technical field

The present invention relates to a sensor chip, and more particularly, to a biosensor chip to easily perform quantitative inspection and detection of chemical materials contained in a sample. Furthermore, the invention relates to a method of manufacturing such a sensor chip. In addition, the present invention relates to a sensor chip, especially a biosensor chip, which is produced by the production method of the present invention.

Background technique

A biosensor chip is a sensor chip that introduces a tracer sample into the reaction part of the chip, causes the tracer sample to produce a biochemical reaction, such as an enzyme reaction or an antigen-antibody reaction, and outputs it as the result of the biochemical reaction. result information. This biosensor chip employs the excellent molecular recognition function possessed by living organisms, and is attracting attention as a chip capable of quickly and easily measuring trace chemical materials. For example, the biosensor chip is used as a blood sugar level sensor for measuring the sugar content in blood (blood sugar level), or as a urine sugar level sensor for measuring urine sugar level, for home health detection (self-care), etc., to Self-manage and protect against diabetes,.

An example of such a sensor chip is described in JP-A-10-2874. This sensor chip has a structure in which a sample is sucked through holes formed in the chip and introduced into a reaction portion. This is a laminated biosensor chip in which a spacer layer having grooves (hollow reaction portions) is provided on a substrate, and a cover layer having air holes is also provided thereon (paragraph 0003). Another example of a laminate type biosensor chip is described in JP-A-11-94790. In this example, an adhesive layer was used to laminate the substrate and cover layer, and the adhesive layer was used as a spacer layer in an attempt to simplify its manufacturing process.

This laminated type biosensor chip is produced by laminating a spacer layer serving as a hollow reaction portion on a substrate, laminating a cover layer thereon, and forming the spacer layer with one or more spacer members. In this case, the spacer member is a single-layer film constituting the spacer layer. The spacer element is bonded to the substrate or cover layer using a pressure-sensitive adhesive material or adhesive, which is also considered to constitute the spacer layer, ie the single layer film of the spacer element.

However, according to the aforementioned laminated type biosensor chip, there is a difference in physical characteristics and a difference in residual stress between layers, and due to these differences, the chip warps over time according to changes in ambient temperature and humidity. When the chip is warped, the appearance deteriorates and the value of the product decreases. Problems also arise such that the volume of the reaction portion may change due to warpage, which adversely affects measured values, and peeling occurs at the interface of the pressure-sensitive adhesive layer. Therefore, there is a need to develop a biosensor chip in which a substrate, a spacer layer, and a cover layer are laminated and in which such warpage does not occur.

Also, by laminating a spacer layer on a substrate, and laminating a cover layer thereon, a biosensor chip described in JP-A-10-2874 or JP-A-11-94790 can be constructed. A hollow reaction part is formed between the substrate and the cover layer by using the spacer layer. After that, when the sample is introduced into the reaction section, biochemical reactions and the like are performed.

For these types of biosensor chips, when bonding the substrate or cover layer to the spacer layer, and when bonding the spacer members constituting the spacer layer (single-layer film constituting the spacer layer) to each other, mainly use A bonding method of a double-sided adhesive tape to which a pressure-sensitive adhesive material is applied or an adhesive method employing a pressure-sensitive adhesive material applied to the surface of a spacer by screen printing, etc. (JP-A-11-94790) . From the standpoint of productivity, pressure-sensitive adhesive materials are preferred because adhesion can be obtained by applying pressure and processes such as heat application or UV radiation are not necessarily required. In addition, since enzymes and the like used in biosensor chips are sensitive to heat application or UV radiation, in this case, it is necessary to use a pressure-sensitive adhesive material as a bonding means as much as possible. However, in order to obtain high adhesion, the pressure-sensitive adhesive material must use a slightly soft and easily deformable material. Therefore, according to temporal transient changes due to residual stress applied during lamination and changes in temperature, humidity, etc. in the environment, dimensions tend to change, and the thickness of the pressure-sensitive adhesive material, etc. also tends to change.

When the thickness of the pressure-sensitive adhesive layer changes after bonding with the pressure-sensitive adhesive material, the distance between the substrate and the cover layer changes, and thus the volume of the hollow reaction portion also changes. When the volume of the hollow reaction portion is changed, problems occur such that the amount of the sample to be introduced into the reaction portion changes and the measured value changes.

On the other hand, in JP-A-11-94791, there is described a biosensor chip constituted by directly bonding a substrate and a cover layer without intervening a spacer layer. This biosensor chip has raised portions on the substrate, and the raised portions are bonded to the cover layer. However, since the substrate and the cover are fixed only through the narrow adhesive portion between the raised portion and the cover without using a spacer, this biosensor is weak in strength and has problems in its reliability. In addition, as another problem, since the entire surface of the cover layer except the bonding portion becomes one face of the hollow reaction portion, the volume of the hollow reaction portion is larger than when the spacer layer is used, and the required sample amount increases.

Therefore, just need to develop a kind of biosensor chip, this biosensor chip adopts spacer layer, promptly this biosensor chip has substrate, cover layer and the spacer layer that is sandwiched between this substrate and cover layer, in application pressure sensitive When the bonding material is used to bond the substrate, the cover layer and the spacer layer, it does not cause the volume change of the reaction part due to the transient change of time or the change of ambient temperature and humidity.

Furthermore, in JP-A-11-94791, it discloses a biosensor chip in which a protruding portion is formed in a substrate, and, through the protruding portion, the substrate is directly bonded to the cover layer so that A hollow reaction part is formed without intervening a spacer layer. A description is given of an example in which an enzyme is contained in the hollow reaction portion on the substrate side and the cover layer side. (paragraph 0021)

As described in this example, since reagents such as enzymes are contained in the sensor chips on the substrate side and the cover layer side, for example, the following better effects (1) to (3) can be obtained. (1) Since the contact area of the sample and the reagent introduced into the reaction section can be enlarged, the reaction period can be reduced. (2) When an enzyme or the like is provided at one location and a surfactant is provided at another location, the sample can be introduced into the reaction section very smoothly due to the surfactant, even if it is relatively difficult to set the introduction port for introducing the sample to the reaction section. Hour. In addition, the sample in the reaction section is evenly distributed, and the inspection cycle and inspection variation can be reduced. (3) Since different types of enzymes that react with different chemical materials are provided at two or more positions, a biosensor chip having a detection function capable of detecting a plurality of chemical materials can be prepared.

On the other hand, a laminate type biosensor chip is disclosed in JP-A-10-2874 or JP-A-11-94791, in which a spacer layer having a hollow reaction portion is placed on a substrate, and a cover layer Override (paragraph 0003). This laminated type biosensor chip has wide application because its productivity is high, and the size of the reaction section and the required sample amount can be reduced.

However, for a conventional laminate type biosensor chip, a cover layer as the upper surface of the biosensor chip and a substrate as the lower surface of the biosensor chip are prepared separately. In order to arrange the reagents in the hollow reaction space on the cover layer side and the substrate side, the reagents must be applied separately. Then, the number of processes is doubled, and productivity deteriorates significantly. Therefore, with the conventional laminate type biosensor chip, it is difficult to arrange reagents such as enzymes on both sides while maintaining high productivity, and a method for solving such a problem is required.

(Patent Document 1) JP-A-10-2874

(Patent Document 2) JP-A-11-94790

(Patent Document 3) JP-A-11-94791

Contents of the invention

The problem to be solved by the present invention

An object of the present invention is to provide a sensor chip, which includes: a substrate; a cover layer; a spacer layer sandwiched between the substrate and the cover layer; and a hollow reaction portion located between the substrate and the cover layer , wherein warpage does not occur due to changes in ambient temperature and humidity or the passage of time. Another object of the present invention is to provide a method of manufacturing such a sensor chip.

Another object of the present invention is to provide a sensor chip comprising: a substrate; a cover layer; a spacer layer sandwiched between the substrate and the cover layer; part, wherein, when a pressure-sensitive adhesive material is used for bonding separate layers, the reaction part does not change in volume according to time transient changes or changes in ambient temperature and humidity.

Another object of the present invention is to provide a sensor chip manufacturing method capable of producing a laminated type sensor chip with high productivity, which is obtained by laminating a substrate, a spacer layer having a hollow reaction portion, and a cover layer A chip, and wherein a reagent is placed in the hollow reaction portion on the cover layer side and the substrate side, and a sensor chip produced by this method are provided.

means of solving problems

As a result of careful studies, the present inventors found that by making the structure of the sensor chip except for the electrode (detection portion) and the reagent application portion having a symmetrical structure with respect to the central plane in the cross-sectional direction of the lamination, the central plane is As an axis, it is possible to obtain a sensor chip in which warpage does not occur due to changes in ambient temperature and humidity or the passage of time, and realize the present invention.

That is to say, the present invention provides a sensor chip, comprising:

Substrate;

cover layer;

a spacer layer sandwiched between the substrate and the cover layer;

a hollow reactive portion disposed between the substrate and the cap; and

a detection part, which is set in the hollow reaction part,

wherein the substrate and cover are made of the same material and have the same thickness, and

The material and shape of the spacer layer are symmetrical about a plane parallel to the substrate and equidistant from the substrate and cover layer.

Since the substrate and cover layer are made of the same material, an insulating material film is selected, and ceramics, glass, paper, biodegradable materials (such as polylactic acid microbial produced polyester), polyvinyl chloride, polyvinyl chloride, etc. Acrylic, polystyrene, polycarbonate, acrylic resins, thermoplastic resins such as polybutylene terephthalate or polyethylene terephthalate (PET), thermosetting resins such as epoxy resins, or plastic materials such as UV curable resins Exemplary as insulating material. Plastic materials such as polyethylene terephthalate are preferred because of the mechanical strength, flexibility, and ease of manufacture and handling of the chip, particularly because of ease of folding, etc., which will be described later.

Preferred thicknesses of the substrate and the cover layer are not particularly limited, wherein the substrate and the cover layer have equal thicknesses, and the thickness thereof may vary depending on the use of the sensor chip. In the case where the biosensor is used as a blood glucose level sensor, it preferably has a thickness of about 100 μm to 300 μm.

The sensor chip of the present invention also includes a spacer layer sandwiched between the substrate and the cover layer. "Sandwiched" means that the spacer layer is bonded on one side to the substrate and on the other side to the cover layer. An electrode layer may also be provided between the spacer layer and the substrate or cover layer.

The sensor chip of the present invention also includes a hollow reaction part between the substrate and the cover layer. The hollow reaction portion is a portion where a sample is introduced and the introduced sample undergoes a chemical reaction when the sensor chip is used. The hollow reaction portion is formed by using grooves of the spacer layer, and, as described below, includes electrodes therein. Also, in the case of using a biosensor chip, reagents such as catalysts and enzymes that induce biochemical reactions are immobilized inside, and thus, the reagents accelerate chemical reactions of samples.

For example, in a glucose biosensor chip for measuring the amount of glucose in blood, a glucose oxidase layer, a glucose oxidase/electron acceptor (mediator) mixed layer, a glucose oxidase/albumin mixed layer, or a glucose A sugar oxidase/electron acceptor/albumin mixed layer and the like are formed in the hollow reaction part. These layers can be formed with enzymes other than glucose oxidase, such as glucose dehydrogenase. Furthermore, as additives, buffers, hydrophilic polymers, etc. may be included in the reagent.

The immobilization of the reagents, that is, the formation of these layers may be performed before the formation of the grooves, which will be described later, or may be performed after the formation of the grooves and before the formation of the hollow reaction portion, or after the hollow reaction portion has been formed. , wherein the groove is formed by bonding a resist member, and the hollow reaction portion is formed by laminating the substrate. Although the ease of execution of the reagent application process and the ease of positioning of the reagent application are considered, it is generally preferable to fix the reagent after the groove is formed and before the hollow reaction portion is formed.

A sample to be measured, such as blood, urine, or a solution sample extracted from a production line, is introduced into the hollow reaction part through the sample introduction port. The sample introduction port can be provided on the substrate or the cover layer, and can be connected to the hollow reaction part through the sample introduction path. The hollow reaction portion opens on at least one side of the spacer layer, and serves as a sample introduction hole. Multiple sample introduction ports can be provided.

In addition, the sensor chip of the present invention has a detection portion within the hollow reaction portion. Here, the detection part includes at least two or more electrodes. These electrodes are often referred to as working electrodes or counter electrodes, and the detection section may include another electrode such as a reference electrode, or other means. The electrode provides operations such as applying a predetermined voltage to the hollow reaction part and measuring a current value received from the hollow reaction part, and based on a signal obtained from the electrode, detection and quantitative testing of chemical materials in a sample are performed.

The electrodes are exposed inside the hollow reaction part, and the lead parts of the electrodes are formed in or between the substrate, the spacer layer, or the cover layer, so that the electrodes are electrically connected to the outside of the sensor chip. Through the lead part, application of a predetermined voltage, measurement of a current value, and the like can be performed.

As described above, in the sensor chip of the present invention, in the laminated cross-sectional direction, structures other than the electrodes and the reagent application portion are symmetrical about the center plane as the axis. This can be obtained by employing a structure in which the substrate and the cover layer are made of the same material and made to be of equal thickness, and, in the cross-sectional direction, the material and shape of the spacer layer are symmetrical about the center plane as the axis. Here, the central plane in the cross-sectional direction is defined as a plane parallel to the substrate (and the cap) and equidistant from the substrate and the cap (hereinafter, the plane is simply referred to as the central plane).

Here, "the material and shape are symmetrical" indicates that the thicknesses on both sides of the central plane are equal, and that the materials equidistant from the central plane are the same. In addition, when the hollow portion, such as a groove, is provided on the spacer layer, the above description is used to define that the shape of the hollow portion along both sides of the central plane is in a mirror image relationship. As described above, in the sensor chip of the present invention, the substrate, cover layer, and spacer layer are symmetrical along the center plane as the axis. As a result, the individual layers are elongated in the same way on both sides of the central plane as a function of changes in ambient temperature and humidity, and thus do not warp over time. It should be noted that the electrode layer and reagent layer become asymmetrical elements when the electrodes (detection portion) and reagents are only applied to the substrate. In this case, too, it was found that warpage did not occur.

Typically, the spacer layer is formed of a single layer of spacer or by laminating multiple layers of spacer. As the material used to form the substrate (and cover layer) and the like, the material used to form the spacer can be used. The spacer (and sheet, which will be described later) can be obtained by bonding such a spacer, or by applying a spacer by a method such as screen printing and curing it as desired. The curing method used may be heat curing or UV curing, and an appropriate method may be selected according to the type of resin used and the like. A pressure sensitive bonding material or adhesive is used to bond the spacer parts together. In addition, pressure-sensitive adhesive materials or adhesives are also used for bonding the spacer layer, the substrate and the cover layer. The layer of pressure-sensitive adhesive material or adhesive used for bonding may also be considered as a spacer member and constitutes the spacer layer.

Methods such as screen printing may also be used to apply the pressure sensitive bonding material or adhesive. A rubber-type pressure-sensitive adhesive material, an acrylic-type pressure-sensitive adhesive material, or a silicon-type pressure-sensitive adhesive material are examples of the pressure-sensitive adhesive material. In addition, epoxy adhesive, vinyl acetate adhesive, or silicon adhesive are exemplified adhesives, and for various materials, heat-curable adhesives or UV-curable adhesives can be employed as curing types. Binder.

In addition, in the process of forming electrodes (and leads) on the substrate (or cover layer) by screen printing, in order to increase the insulating properties between the electrodes and physically protect the electrodes, a resist material can be used on the substrate (or cover layer). A resin layer called a resist layer is formed on the cover layer) to cover the electrodes (and lead wires) except for the part exposed to the hollow reaction part. Urethane resins, epoxy resins, denatured polyimide resins, acrylic resins, and the like can be used as such a resist material. This resist layer is also regarded as a spacer and constitutes a spacer layer.

When the spacer layer is formed of a plurality of spacer members including layers such as a pressure-sensitive adhesive material and an adhesive, individual spacer members may differ in material, thickness, and the like under the following conditions. However, in the sensor chip of the present invention, since the spacer layer must be symmetrical about the center plane, the two spacer members placed on both sides of the center plane and equidistant from the center plane have equal thickness and are made of the same material. This spacer layer is obtained by bonding sheets with grooves, wherein the material, thickness and position of the grooves are the same, so that the grooves are aligned and symmetrical with respect to the bonding plane.

The lamellae are the layers that make up the spacer layer, and are the layers located on either side of the central plane. The sheet layer may be a single layer of spacer, or a laminated structure of multiple layers of spacer. The sheet can be formed by applying and curing a resist material, a pressure-sensitive adhesive material, an adhesive, etc. to a substrate, and by laminating a spacer to the substrate, or by laminating a plurality of spacers. A resist material, a pressure-sensitive adhesive material, or an adhesive may be used for the laminated structure of the spacer, and a layer of the resist material, pressure-sensitive adhesive material, or adhesive may be regarded as the spacer, and constitute a sheet. The space obtained by aligning the grooves forms a hollow reaction portion. It should be noted that in order to align the grooves, the shape of the grooves must be mirrored. It is preferable that the individual grooves are formed linearly, taking into account ease of manufacture and ease of reagent application.

Furthermore, the present invention provides a sensor chip in which a spacer layer is formed by bonding a pair of sheets together, wherein the spacer layer has grooves and is made of a single-layer or multi-layer spacer member,

each ply of the ply pair is formed from the same material and is of the same thickness, and

The pair of plies is bonded together so as to be symmetrical about a plane.

For example, the sensor chip of the present invention can also be obtained by bonding the sheets to a substrate sheet serving as the base sheet and the cover layer, and by folding the substrate sheet along fold lines which The sheet is divided into two approximately equal parts so that the two parts of the sheet face each other. In this case, the substrate plate used as the substrate and the cover layer is the part that becomes the substrate and the cover layer after the sensor chip is prepared.

In the method of folding along the fold line, in addition to the method of folding at the position of the fold line, there is provided a method of folding at the position of two straight lines so as to obtain a U-shaped cross section, wherein the two straight lines Parallel to and equidistant from the polyline. A pressure-sensitive bonding material or adhesive is used to bond portions of the sheet and is used to bond the sheet to the substrate, and the layer of such pressure-sensitive bonding material or adhesive is also visible as a spacer and form a spacer layer. Since the layer placed on the center plane does not warp, there is no problem when the layer is not paired. Thus, the layers of pressure-sensitive adhesive material and adhesive used to bond portions of the sheets need not be paired. Of course, the spacer member placed on the uppermost surface of the sheet may have an adhesive function, so it is possible to be able to bond without the use of pressure-sensitive adhesive materials or adhesives.

The sheet includes a pair of grooves symmetrical about a fold line serving as an axis, and is bonded to the substrate plate, so that at least one of the grooves includes a detection portion, ie, an electrode. Therefore, when folded along the fold line, the grooves are aligned, and a hollow reaction portion including a detection portion (electrode) is formed therein.

Also, the present invention provides a sensor chip in which, after forming a laminated body by laminating sheets on substrate plates serving as a base and a cover, the sheets have a symmetric shape with respect to a broken line serving as an axis. For grooves, the fold line divides the substrate plate into two roughly equal parts, therefore, at least one of the grooves includes a detection portion,

folding the laminate along the fold line so that the pair of grooves are aligned with each other to form a hollow reactive portion, and

bonding the parts of the sheet together,

Thus, a sensor chip was obtained.

In one example, the paired grooves are symmetrical along a fold line which may be curved or along a fold line in mirror image relationship. However, while considering ease of manufacture and ease of reagent application, it is preferable that the individual grooves are shaped linearly, in parallel, and at positions at equal distances from the fold lines. Furthermore, the present invention provides a sensor chip, wherein the pair of grooves are parallel to each other and formed linearly.

The sensor chip employing the present invention is particularly useful as a biosensor chip, preferably a blood sugar level sensor for measuring glucose level (blood sugar level) in blood, a urine sugar level sensor for measuring urine sugar level, and the like. As described above, the present invention provides a sensor chip, wherein the sensor chip is a biosensor chip.

Additionally, the present invention provides a method of manufacturing the above-mentioned sensor chip. In particular, there is provided a method for manufacturing a sensor chip having a substrate, a cover layer, a spacer layer sandwiched between the substrate and the cover layer, a hollow reaction portion disposed between the substrate and the cover layer, and The detection part provided in the hollow reaction part, the method includes:

forming a detection portion on a substrate plate serving as a substrate or a cover layer; and

bonding laminate 1 and laminate 2 so that the sheets of laminate 1 and laminate 2 face each other and the grooves of the sheets are aligned with each other, thereby forming a hollow reaction portion,

Wherein, the laminated body 1 is obtained by forming a sheet having a groove and made of a single-layer or multi-layer spacer member, and therefore, the detection portion is contained in the groove, and

The substrate board and the plies of the laminate 2 were made of the same material, and their thickness and configuration were the same as those of the laminate 1 .

This is a method of bonding laminates consisting of identical substrate sheets and identical plies facing each other. In this case, "the same structure" means that the number of spacer members (including pressure-sensitive adhesive materials, etc.) constituting the sheet and their materials, lamination order, position, size and shape of the grooves are consistent, or are Mirror relationship. A pressure sensitive adhesive material or adhesive may be used to bond the sheets, or the topmost surface of the sheets may be made tacky so that they are bonded directly. In addition, the detection portion may or may not be formed in the laminated body 2 .

The present invention provides a method for manufacturing a sensor chip having a substrate, a cover layer, a spacer layer interposed between the substrate and the cover layer, a hollow reaction part provided between the substrate and the cover layer, The detection part provided in the hollow reaction part, the method includes:

forming a detection portion on a substrate plate serving as a substrate and a cover layer;

A laminate is formed by laminating sheets having a pair of grooves which are symmetrical with respect to a fold line as an axis so that at least one of the grooves contains a detection portion therein, and the sheet is a spacer member or a plurality of a laminate of spacer members, and a fold line dividing the substrate sheet into two substantially equal parts;

After the laminate is formed, the laminate is folded along the fold lines so that the sheets face each other; and

Bond the sheets together.

According to this method, a pair of grooves in a sheet layer are symmetrical about a fold line as an axis, and the sheet is then folded along the fold line. Thus, as the sheets are folded and glued together, the grooves are aligned and a hollow reaction portion is formed.

Furthermore, the present inventors found that the above object can be achieved by stably connecting and fixing the substrate and the cover layer at their one ends so that the distance between them does not change and completed the present invention.

The invention provides a sensor chip, which includes:

Substrate;

cover layer;

a spacer layer sandwiched between the substrate and the cover layer;

a hollow reactive portion disposed between the substrate and the cap; and

The detection part provided in the hollow reaction part, wherein

The substrate and the cover are connected to each other at one end of the substrate and at one end of the cover, and are integrally formed.

The substrate and the cover layer can be formed of different materials as long as they can be stably connected together. However, it is preferable to use the same materials in order to easily obtain a stable connection therebetween. An insulating film material can be selected as the material, and exemplary insulating materials can be ceramics, glass, paper, biodegradable materials (e.g., polylactic acid microbially produced polyester), polyvinyl chloride, polypropylene, polystyrene, poly Carbonate, acrylic resins, thermoplastic resins such as polybutylene terephthalate or polyethylene terephthalate (PET), thermosetting resins such as epoxy resins, or plastic materials such as UV curable resins. Plastic materials such as polyethylene terephthalate are preferred because of the chip's mechanical strength, flexibility and ease of manufacturing and handling the chip, especially because of the ease of folding, as will be described later.

The substrate or cover layer can be of the same or different thickness. The preferable thickness ranges of the substrate and the cover layer vary depending on the use of the sensor chip and the like, and are not particularly limited thereto. In the case where the biosensor chip is used as a blood sugar level sensor, it is preferably 100 μm to 300 μm.

The sensor chip of the present invention also includes a spacer layer sandwiched between the substrate and the cover layer. "Sandwich" means that the spacer layer is bonded on one side to the substrate and on the other side to the cover layer. Another layer such as an electrode may also be provided between the spacer layer and the substrate or cover layer. For bonding, pressure-sensitive adhesive materials such as double-sided adhesive tape can be used. In the present invention, changes in the thickness of the chip with the lapse of time or the like can be suppressed even when the pressure-sensitive adhesive material is used.

The spacer layer may be formed from one spacer or a laminate of multiple spacer members. The individual spacer elements of the multilayer spacer elements may differ from one another. The same materials as those used for the substrate and cover layer in Examples can be used as the material for the spacer layer. For example, these materials and the pressure-sensitive adhesive material can be applied by screen printing to the substrate and another spacer, after which the topmost spacer is bonded to the cover layer, thus forming a sandwich between the substrate and cover. Spacer layer between layers. When the spacer layer is made in this way from multiple layers of spacer members, a pressure sensitive adhesive material can be used to bond the spacer members together. As in the case of the above, in the present invention, when the pressure-sensitive adhesive material is used, it is still possible to suppress the chip thickness from changing with the lapse of time.

The chip of the present invention also includes a hollow reaction part between the substrate and the cover layer. The hollow reaction portion is a portion in which a sample is introduced and the introduced sample is caused to undergo a chemical reaction when the sensor chip is used. The hollow reaction part is formed by the recess of the spacer layer and, as described below, the electrodes are contained therein. Furthermore, in the case of using a biosensor chip, reagents that induce chemical reactions such as catalysts and enzymes are immobilized inside, and thus, the reagents accelerate chemical reactions of samples.

Furthermore, in the case of using a biosensor chip for measuring the amount of glucose in blood, a glucose oxidase layer (GOD), a glucose oxidase/electron acceptor (mediator) mixture layer, a glucose oxidase/albumin mixture layer, glucose oxidase/electron acceptor/albumin mixture layer, etc. are formed in the hollow reaction part. These layers can be formed by using enzymes other than glucose oxidase, such as dehydrogenase (GDH) or the like. In addition, as additional reagents, buffers, hydrophilic polymers, etc. may be included in the reagents.

A sample to be measured such as blood, urine, or a solution sample extracted from a production line is introduced into the hollow reaction part through the sample introduction port. The sample introduction port is provided on the substrate or the cover layer, and is connected to the hollow reaction part through the sample introduction path. The hollow reaction portion is opened on at least one side of the spacer layer, and serves as a sample introduction port. Multiple sample introduction ports can be provided.

In addition, the sensor chip of the present invention has a detection portion inside the hollow reaction portion, that is, the detection portion is exposed inside the hollow reaction portion. Here, the detection part includes at least two or more electrodes. These electrodes are often referred to as working or counter electrodes, and the detection section may include another electrode such as a reference electrode, among other devices. These electrodes provide operations such as applying a predetermined voltage to the hollow reaction portion and measuring a current value received from the hollow reaction portion, and based on signals obtained from the electrodes, detection and quantitative examination of chemical materials in a sample are performed.

The electrodes are exposed inside the hollow reaction part, and leads of the electrodes are formed in or between the substrate, the spacer layer, or the cover layer, so that the electrodes can be electrically connected to the outside of the sensor chip. Through the lead part, it is possible to apply a predetermined voltage, measure a current value, etc.

In the sensor chip of the present invention, the substrate and the cover layer can be connected at their one ends and formed integrally. "To be connected and integrally formed" means to be connected so that the positional relationship between the two does not change. Therefore, the distance between the substrate and the cover layer is fixed and does not change in this part. As a result, the variation of the distance between the substrate and the cover layer in the hollow reaction part is suppressed, and the volume change of the reaction part with time transient change or ambient temperature or humidity change (which is a problem of the prior art) is also suppressed. inhibition.

In a general sensor chip, the hollow reaction portion is provided at a position close to one end of the sensor chip instead of close to the center of the sensor chip. Therefore, it is preferable to select the end close to the hollow reaction part as the end, and the substrate and the cover layer are stably connected and integrally formed at this end, because the volume change of the hollow reaction part is suppressed more effectively.

The method of obtaining the substrate and cap layer connected at one end and integrally formed is not particularly limited. For example, when the base sheet and the cover layer are formed of thermoplastic resin, a method of melting and bonding them at this portion may be used, or a method of bonding them together using a strong adhesive may also be used.

In particular, it is preferable to adopt a method in which a base sheet is folded along a fold line dividing the base sheet into two approximately equal parts, and one side of the fold line is used as the base sheet and the other side is used as the cover sheet , this is because the sensor chip is easy to manufacture and a stable fixed connection can be obtained. The invention provides a sensor chip obtained by said preferred method and wherein the substrate and the cover layer are formed by folding the substrate sheet along a fold line dividing the substrate sheet into two substantially equal parts .

In the method of folding along the fold line, in addition to the method of folding at the position of the fold line, it also includes the method of performing folding at the positions of two straight lines parallel to the fold line and equidistant from the fold line, so as to obtain a U-shaped cross section .

The sensor chip employing the present invention is used as a biosensor chip, preferably a blood sugar level sensor for measuring glucose level (blood sugar level) in blood, a urine sugar level sensor for measuring urine sugar level, and the like. The present invention relates to this preferred aspect, and provides the above-mentioned sensor chip, wherein the sensor chip is a biosensor chip.

Preferably, the sensor chip is manufactured by a method in which the substrate and cover are formed by folding a substrate sheet along a fold line that divides the substrate sheet into two approximately equal parts. The present invention also provides a method of manufacturing a sensor chip related to these preferred aspects.

In particular, the present invention provides a method for manufacturing a sensor chip having a substrate, a cover layer, a spacer layer sandwiched between the substrate and the cover layer, and a hollow space between the substrate and the cover layer. The reaction part, and the detection part arranged in the hollow reaction part, the method includes:

A detection portion is formed on at least one side of a substrate sheet and a fold line that divides the substrate sheet into two substantially equal parts;

Fold the substrate board along the crease line;

inserting a spacer layer having grooved portions between the folded substrate panels; and

A spacer layer is bonded to the folded substrate sheet in order to obtain a laminate.

Additionally, the present invention provides a method for manufacturing a sensor chip having a substrate, a cover layer, a spacer layer sandwiched between the substrate and the cover layer, a hollow space between the substrate and the cover layer. The reaction part, and the detection part arranged in the hollow reaction part, the method includes:

A detection portion and a spacer layer having a groove portion are formed on at least one side of the substrate sheet and a fold line that divides the substrate sheet into two substantially equal parts;

folding the substrate sheet over along the fold line; and

The spacer layer and the other side of the substrate sheet are bonded to obtain a laminate.

The method of the present invention is a method of forming an integral substrate by folding a substrate plate on which a detection portion is formed so as to divide the substrate into two approximately equal parts, and by forming a spacer layer having a hollow reaction portion The folded substrate is inserted to bond the spacer layer. Another method of the present invention is to form a spacer layer having a hollow reaction portion on one side of a line that divides a substrate plate into approximately equal two parts, a detection portion is formed on one substrate plate, and thereafter, along The wire folds over the substrate sheet to bond the spacer layer and the substrate.

As mentioned above, the spacer layer may be formed by lamination prior to the folding process, or by insertion after the folding process. When the spacer layer is inserted after the substrate sheet is folded, insertion is made difficult when pressure sensitive adhesive material is present in the portion where the substrate and cover layer and/or spacer layer are bonded prior to insertion. Therefore, it is preferable to use a heat-curing, UV-curing adhesive or the like instead of the pressure-sensitive adhesive material, and to bond and fix the spacer, substrate, and cover layer by applying heat or radiating UV after inserting the spacer.

For the method of laminating after folding the substrate or the method of inserting after folding the substrate, it is preferable to use a substrate sheet made of thermoplastic resin and, after folding, perform a heat process for the folded portion (thermal process). Through the thermal process, since residual stress due to folding is removed and the folded portion is fixed, changes in the positional relationship between the substrate and the cover layer due to the lapse of time or the like can be suppressed more effectively. As described above, the present invention provides a method of manufacturing a sensor chip,

wherein the substrate plate is made of thermoplastic resin, and

After the substrate sheet is folded, a thermal process is performed on the folded portion.

As mentioned above, also included in the folding process is the method of performing the folding in order to obtain a U-shaped cross-section. When a thermoplastic resin such as PET is used as the substrate sheet, a particularly preferable folding method is to fold the substrate sheet made of thermoplastic resin into a U shape by folding the substrate sheet while applying heat as in flat press molding, and then perform thermal process, due to which precise and economical manufacture can be obtained. At this time, when a plurality of holes (so-called perforations) are partially formed, or a groove (so-called half-cut) is preformed along the fold line of the substrate sheet, and the substrate sheet is folded later, the folding accuracy is increased . It should be noted that the method of using one groove is more preferable than the method of forming a plurality of holes in order to maintain a high fixing strength of the substrate and the cap layer.

In the case of using a biosensor chip, reagents including enzymes and the like are embedded in the hollow reaction portion on the substrate and the cover layer. Depending on the method of laminating the spacer layer on the substrate sheet prior to folding, the placement of the reagents can be performed before or after folding the substrate sheet.

However, it is often difficult to apply and set up reagents, for example using a dispenser, after the substrate sheet has been folded. Therefore, a method in which reagents are provided on a substrate plate prior to folding is preferable from the viewpoint of productivity. On the other hand, when the setting of the reagent is performed before the substrate sheet is folded, the reagent such as the enzyme will be deteriorated by heat during the execution of the heat process for the folded portion. Therefore, when the heat resistance of a reagent such as an enzyme is low, a process such as setting the reagent setting area out of the heat area is required. It should be noted that, in order to simplify the positioning of the reagents to be positioned, the method of positioning the reagents will be carried out after the spacer layer has been laminated and not before lamination of the spacer layer.

It is generally preferred that the temperature for the thermal process of the thermoplastic resin is equal to or higher than the middle value of the resin softening temperature (glass transition temperature) and melting point, and equal to or lower than the melting point. When the thermal process temperature is lower than the middle value of the softening temperature and the melting point of the resin, the residual stress of the folded portion is not properly removed, and the folded portion may change with the lapse of time. On the other hand, when the thermal history temperature exceeds the melting point, resin deformation increases and a smooth folded surface cannot be maintained. Since the resin softening temperature of PET resin is about 70°C and the melting point is about 250°C, it is preferable that the heat history temperature of the folded portion is equal to or higher than 160°C for the substrate sheet made of PET resin, and equal to or lower than 250°C. Generally, the PET resin may be Melinex or Tetoron (product name, Toray Dupont Films Japan, Ltd.), Lumirror (product name, Toray Industries, Inc.), or the like. On the other hand, since an enzyme such as GOD or GDH deteriorates at a temperature of 60°C or higher, it is preferable that for a biosensor chip using such an enzyme, such as adjusting the temperature of the thermal process and hollowing out The reaction part is spaced an appropriate distance from the broken line and so on, so that the setting part of the enzyme is not equal to or higher than 60°C.

In any of the manufacturing methods described above, in performing the method for one sensor chip, the productivity is low, and the difference in the distance between the substrate and the cover layer differs for each sensor chip used. As a result, problems such as an increase in the volume change of the reaction portion and an increase in the change in the measured value occur. Therefore, as a preferable method, it is possible to use a single substrate board corresponding to a plurality of sensor chips, and simultaneously form a plurality of pairs of detection parts, and perform the above-mentioned manufacturing method. Then, a plurality of sensor substrates are formed on a single substrate sheet, and the substrate sheet is then diced into individual sensor chips. By using this method, productivity is improved, and a plurality of sensor chips are manufactured in a series of subsequent steps, and therefore, changes in the volume of the reaction section and the like can be prevented.

When forming the detecting portion according to this method, a plurality of pairs of detecting portions are formed so as to be arranged in parallel to the direction of the folding line. Here, the pair of detection sections is a pair of electrodes corresponding to the detection section of an individual sensor chip and including at least two electrodes called a working electrode and a counter electrode. At the time of folding, the formation of the spacer layer, the insertion of the spacer layer, etc. as described above are performed with respect to one substrate sheet on which a plurality of pairs of detection parts are formed, and a laminated body is obtained in which a plurality of sensor chips are arranged along the Connect in a direction parallel to the polyline.

By cutting the laminate along one or more straight lines perpendicular to the fold lines, a plurality of individual sensor chips can be obtained. Cutting is performed so that at least one pair of detection sections is included in each cut out chip. As described above, the present invention provides a method of manufacturing a sensor chip, further comprising:

forming multiple pairs of detection parts, and simultaneously arranging the detection parts parallel to the direction of the broken line; and

Cutting of the obtained laminate is performed along one or more lines perpendicular to the fold lines so that at least one pair of detection sections is included in each sensor chip.

Furthermore, as a result of consideration, the present inventors have found that the above object can be achieved by the structure described below, and the present invention has been achieved.

In particular, the present invention provides a method of manufacturing a sensor chip having folded substrates, a spacer layer sandwiched between the folded substrates, a hollow reaction portion provided between the folded substrates, and a In the detection section within the hollow reaction section, the method includes:

The laminated body 1 is formed by laminating a sheet having a pair or more than one pair of grooves axisymmetric with respect to a crease line serving as an axis to a substrate on which a detection portion is formed. the substrate is divided into two substantially equal parts, whereby at least one groove contains the detection portion;

simultaneously applying reagents to the substrate at locations corresponding to individual wells of the pair of wells; and

After two steps, the laminate 1 is folded along the fold lines and the parts of the plies are bonded to form the spacer layer.

The sensor chip manufactured by the manufacturing method of the present invention is a sensor chip including folded substrates, a spacer layer sandwiched between the substrates, a hollow reaction portion between the substrates, and a detection portion within the hollow reaction portion. The folded substrate corresponds to the substrate and cover layer of prior art sensor chips of the laminated type. Since the substrate and cover layer can be obtained from a single substrate, the two are connected at one end and are made of the same material and of equal thickness. Insulating film materials can be selected as the material, and exemplary insulating materials can be ceramics, glass, paper, biodegradable materials (such as polyester produced by polylactic acid microorganisms), polyvinyl chloride, polypropylene, polystyrene, poly Carbonates, acrylic resins, thermoplastic resins such as polybutylene terephthalate or polyethylene terephthalate (PET), thermosetting resins such as epoxy resins, or plastic materials such as UV curable resins. This is because of the mechanical strength, flexibility and ease of manufacture and handling of the chip, and especially because of the ease of folding, which will be described later, a plastic material such as polyethylene terephthalate is preferred. The preferred thickness ranges of the substrate and cover layer vary depending on the use of the sensor chip and the like, and are not particularly limited thereto. In the case of a biosensor chip such as a blood sugar level sensor, it is preferably about 100 μm to 300 μm.

The substrate is folded along a crease line that divides the substrate into two approximately equal parts when the substrate is opened. The spacer layer is sandwiched between the folded portions of the substrate. In the method of folding along the fold line, in addition to the method of folding at the position of the fold line, it also includes the method of folding along the positions of two straight lines parallel to the fold line and equidistant from the fold line, so as to obtain a U-shaped transverse section.

"The spacer layer is sandwiched between the folded portions of the substrate" means that both surfaces of the spacer layer are bonded to the folded portions of the substrate. Another layer, such as an electrode, may be provided between the spacer layer and the substrate.

According to the sensor chip manufactured by the manufacturing method of the present invention, the hollow reaction portion is formed between the folded portions of the substrate. The hollow reaction portion is a portion into which a sample is introduced and causes a chemical reaction of the introduced sample when the chip is used. A hollow reaction portion is formed using grooves of the spacer layer, and electrodes are contained therein as described below. Also, in the case of using a biosensor chip, reagents that induce chemical reactions such as catalysts and enzymes are immobilized inside, and thus the reagents accelerate chemical reactions of samples. In the present invention, reagents are provided on the upper and lower surfaces of the hollow reaction portion, that is, on both sides of the pair of grooves formed in the folded substrate.

In the case of using a biosensor chip, reagents such as catalysts and enzymes to be provided are reagents for causing biochemical reactions, and various types of auxiliary agents may be included to smoothly generate such biochemical reactions. More specifically, in the case of using a glucose biosensor chip that measures the amount of glucose in blood, for example, glucose oxidase (GOD), glucose oxidase/electron acceptor (mediator) mixture can be used , glucose oxidase/albumin mixture, glucose oxidase/electron acceptor/albumin mixture layer, etc. For example, enzymes other than glucose oxidase, such as glucose dehydrogenase (GDH), may also be used. Furthermore, as additives, buffers, hydrophilic polymers and the like may be contained in the reagents.

A sample to be measured, such as blood, urine, or a solution sample extracted from a production line, is introduced into the hollow reaction part through the sample introduction port. The sample introduction port may be provided in the substrate or the cover layer, or may be connected to the hollow reaction part via a sample introduction path. The hollow reaction part can be opened on at least one side of the spacer layer and used as a sample introduction port. Multiple sample introduction ports can be provided. It is particularly preferred that the hollow reaction portion extends through the spacer layer, and the openings at both ends can be used as sample introduction ports. Since the hollow reaction part is shaped like a straw, the sample can be easily introduced into the hollow reaction part by capillary phenomenon.

In addition, the sensor chip manufactured by the manufacturing method of the present invention has a detection part in the hollow reaction part. Here, the detection part includes at least two or more electrodes. These electrodes are often referred to as working or counter electrodes, and the detection section may include another electrode such as a reference electrode, among other devices. The electrode provides operations such as applying a predetermined voltage to the hollow reaction portion and measuring a current value received from the hollow reaction portion, and based on signals obtained from the electrodes, detection and quantitative examination of chemical materials in a sample are performed.

The electrodes are exposed inside the hollow reaction part, and the lead parts of the electrodes are formed in or between the substrate, the spacer layer, or the cover layer, so that the electrodes can be electrically connected to the outside of the sensor chip. Through the lead part, a predetermined voltage can be applied, a current value can be measured, and the like.

In the manufacturing method of the present invention, usually, the above-mentioned detection portion is formed on the substrate before folding. The detection part can be formed by screen printing, electroplating, evaporation, metal tape bonding and other methods. The detection part may be formed on only one side of the fold line, or formed on both sides of the fold line. Also, when a plurality of sensor chips is manufactured through a series of steps, a plurality of pairs of detection portions are formed and arranged parallel to the fold line direction. Here, a pair of detection sections is a pair of electrodes included in one sensor chip, and includes at least two electrodes, a working electrode and a counter electrode.

The sheet was laminated on the substrate at the position where the detection portion was formed, and a laminated body 1 was obtained. The sheet is a laminate formed of a single-layer spacer or a multi-layer spacer, and in the present invention, the spacer is formed by bonding two sheets. The spacer member is a single-layer film constituting the spacer layer.

The sheet comprises one or more pairs of grooves, ie two or more grooves, mutually axisymmetric about a fold line serving as an axis. The substrate and the sheet are laminated so that at least one groove of the sheet includes a detection portion, ie the electrodes are exposed in the groove.

Since two or more grooves in the sheet are located in the same plane, two or more grooves can be formed in the same process, and productivity can be improved compared to the case where the grooves are formed independently. As a method of laminating the sheets and forming the grooves, for example, a tape with a pressure-sensitive adhesive layer can be bonded to a substrate on which the detecting portion is formed, and the two grooves can be obtained.

However, in consideration of productivity, a method of applying resin using a method such as screen printing is preferable because a sheet having one or more pairs of grooves can be laminated to on the substrate. According to this method, two grooves can be easily formed with the same process load as that required to form one groove, just by simply changing the shape of the printing plate. As described above, the present invention provides a method of manufacturing a sensor chip in which a sheet having more than one pair of grooves can be laminated in one step by applying a resin to the substrate, wherein the grooves The groove is axisymmetric about a broken line serving as an axis.

According to the manufacturing method of the present invention, reagents such as catalysts or enzymes can be applied to the positions on the substrate corresponding to the grooves. As described above, there are at least two grooves, and in the manufacturing method of the present invention, reagents are simultaneously applied to portions corresponding to the at least two grooves. In traditional manufacturing methods, the reagents are applied to the two parts separately, and thus the productivity is low. However, according to the present invention having the arrangement as described above, simultaneous operations can be performed at two positions, and as a result, high productivity is obtained.

Through the step of laminating the sheets and the step of applying the reagent, a laminate is obtained in which two or more grooves are formed on the substrate and the reagent is applied in the two or more grooves. Afterwards, this laminate is folded along the fold lines. As mentioned above, the laminate can be folded so as to obtain a U-shaped cross-section. Then, a plurality of parts of the sheet is superimposed, and the overlapped parts of the sheets are bonded, thereby obtaining a spacer layer, and a sensor chip in which the spacer layer is sandwiched between the folded parts of the substrate is manufactured. Furthermore, when the laminate is folded along the fold line, the pair of grooves of the sheet align and form a hollow reaction portion. Since the reagents have been individually applied into the pair of grooves, the reagents are disposed on the upper and lower surfaces of the hollow reaction portion.

A sheet lamination step or a reagent application step is performed first. As an example of the present invention, a reagent application step is performed first, and a sensor chip manufacturing method is provided in which, after application of a reagent, a laminate 1 is obtained by forming a sheet having a pair of grooves. According to this method, after the reagent is applied, the sheet is formed by a method such as bonding a sheet member around the reagent or applying a resin around the reagent.

Furthermore, as another example of the present invention, a sheet lamination step is performed first, and a method of manufacturing a sensor chip is provided in which, after the laminated body 1 is obtained by forming a sheet having a pair of grooves, applying reagent. According to the method in which the sheet lamination step is performed first, the region of the hollow reaction portion can be clearly identified before folding. Therefore, this method is preferable from the viewpoint of ease of manufacture because the application region and application position of the reagent can be easily determined before the reagent is applied, and is also preferable because a high-quality biochip can be manufactured.

Two parallel linear grooves are preferably as a pair of grooves in the sheet, the pair of grooves being axisymmetric about a fold line used as an axis, wherein the two parallel linear grooves are equidistant from the fold line prior to folding . In this case, a coater having a simple structure in which two nozzles are fixed can simultaneously coat positions corresponding to two grooves. That is, in this case, for example, a coater having two nozzles for coating the upper surface and the lower surface with a fixed distance between the two nozzles and coating The machine or laminate moves parallel to the grooves, whereby the reagents can be applied sequentially and simultaneously on both application surfaces. Therefore, this step is very economical. As described above, the present invention provides a method of manufacturing a sensor chip in which the grooves of the groove pair are parallel and formed linearly.

The reagents to be applied to the two or more grooves can be the same or different. As described above, when the enzyme is applied to one groove and the surfactant is applied to the other groove, the sample can be introduced into the reaction layer extremely smoothly when the sample introduction port is small. In addition, the sample can be uniformly distributed in the reaction section, the inspection cycle can be reduced, and the variation in inspection can also be effectively reduced. When the same enzyme is applied on both surfaces, the contact area of the sample and the enzyme is increased, thus, the reaction period of the sample and the enzyme can be reduced. In addition, when different types of enzymes that react with different chemical materials are applied to the two surfaces, a biochip with multiple sample detection functions can be prepared.

According to the present invention, in the above-mentioned coater, when different nozzles are used for different reagents, different reagents can be applied without increasing the load applied to the process. As an example of the present invention for applying different reagents, there is provided a method of manufacturing a sensor chip in which different reagents are simultaneously applied to positions corresponding to respective grooves of a groove pair.

In any of the above-mentioned manufacturing methods, when the method is used for one sensor chip, the productivity is low, and the difference in the distance between the substrate and the cover layer varies from chip to chip. As a result, there arises such a problem that the volume change of the reaction portion increases, and the deviation of the measured value increases. Therefore, as a preferable method, the above-mentioned manufacturing method can be performed by using a single related large substrate plate that becomes the substrate of a plurality of sensor chips, and forming multiple pairs of detection parts at the same time. That is, the respective substrates of the respective sensor chips are connected. A plurality of sensor chips are then formed on a single substrate sheet, after which the substrate sheet is diced into individual sensor chips. With this method, productivity is improved, and a plurality of sensor chips can be manufactured after a series of steps, and therefore, changes in the volume of the reaction portion and the like can be prevented.

According to this method, a plurality of pairs of detection parts are formed and arranged parallel to the fold line direction. In addition, the substrate has a size and shape capable of forming a plurality of pairs of detecting portions so as to be arranged parallel to the fold line direction. Also, the size of the sheet, the location where the reagent is applied, etc. correspond to the size. When the operations of laminating the sheet layers, applying the reagents, and then folding the substrate as described above are performed with respect to one substrate plate on which a plurality of pairs of detection parts are formed, a laminated body in which a plurality of sensor chips are parallel to the fold line can be obtained Orientation is set and connected.

By cutting this laminate along one or more straight lines perpendicular to the fold line, the individual sensor chips are separated and a plurality of sensor chips are obtained. Cutting is performed such that at least one pair of detection sections is included in each cut out sensor chip. That is to say, the present invention provides a method for manufacturing a sensor chip, wherein the detection parts formed on the substrate include multiple pairs of detection parts arranged parallel to the fold line direction, and

The manufacturing method also includes:

The formed laminated body 2 is cut along one or more straight lines perpendicular to the fold lines so that at least one pair of detection sections is included in each sensor chip.

According to the method of manufacturing a plurality of sensor chips, the cutting of the individual sensor chips is performed after the folding step and the sheet bonding step. With this method, dust generated during cutting can be prevented from entering the reaction portion as foreign matter. Additionally, this method is also relatively advantageous in terms of productivity since the folding steps can be performed simultaneously. Furthermore, in the plurality of sensor chip manufacturing methods, it is preferable that the reagent applying portion located at the groove or a position corresponding to the groove is linearly arranged. With this arrangement, for the same reason as described above, the coater can be easily operated, and the nozzle can be moved smoothly within a minimum moving distance. Therefore, economical manufacturing is possible.

It should be noted that, as another method of providing high productivity, there may also be employed a method in which a plurality of sets of multiple detecting portions arranged parallel to the fold line direction are formed on one substrate plate, and in a direction perpendicular to the fold line, Sheet lamination and groove forming are performed in the same manner as above, and reagent application is also performed in the same manner as above, after which the individual groups can be separated by cutting the substrate sheet in the direction of the fold line, The groups are then folded and then cut to obtain individual sensor chips.

The present invention provides a sensor chip manufactured by the above manufacturing method. That is, the present invention relates to such a sensor chip. Such a sensor chip is particularly useful as a biosensor chip, preferably a blood sugar level sensor for measuring a glucose level (blood sugar level) in blood, a urine sugar level sensor for measuring a urine sugar level, and the like. Claim 9 relates to this preferred aspect and provides the above-mentioned sensor chip, wherein the chip is a biosensor chip.

Advantages of the invention

By using the central plane as the axis in lamination, the structure of the sensor chip of the present invention can be formed symmetrically. As a result, a reliable sensor chip can be obtained in which warpage does not occur in the cross-sectional direction and its appearance is satisfactory without surface peeling of the pressure-sensitive adhesive material or the like or deviation in measured values . In particular, the sensor chip can be suitably used as a biosensor chip such as a blood sugar level sensor. According to the sensor chip manufacturing method of the present invention, such an excellent sensor chip can be easily manufactured.

Moreover, in the sensor chip of the present invention, the sensor chip includes a substrate, a cover layer, and a spacer layer sandwiched between the substrate and the cover layer, the substrate and the cover layer are integrally formed, and the positional relationship between the two is fixed. fixed. Therefore, when a pressure-sensitive adhesive material is used to bond separate layers, etc., the distance between the substrate and the cover layer does not change, and the volume of the reaction portion rarely changes due to temporal transient changes, ambient temperature and humidity changes . Since the volume of the reaction section is thus stable, the measurement results obtained based on these conditions are also stable and very reliable.

Additionally, by using the manufacturing method of the present invention, the sensor chip of the present invention can be easily manufactured. In particular, according to the method in which a plurality of sensor chips are formed on one substrate board and then individual sensor chips are obtained by cutting the substrate board, the sensor chips can be precisely and economically manufactured. The sensor chip obtained in this way is suitable as a biosensor chip such as a blood glucose level sensor.

Also, by using the manufacturing method of the present invention, a laminated type sensor chip in which a spacer layer is sandwiched between substrates and a reagent is provided to the upper surface of the hollow reaction portion formed between the substrates can be obtained with high productivity. and on the lower surface. That is, according to the production method of the present invention, the reagent can be applied to both surfaces of the hollow reaction part in one process, and the productivity reduction due to the application of the reagent to two positions does not occur, which is a traditional problem.

Description of drawings

FIG. 1 is an explanatory diagram showing one example of a sensor chip and its manufacturing method according to the present invention.

FIG. 2 is an explanatory diagram showing another example of a sensor chip and its manufacturing method according to the present invention.

FIG. 3 is an explanatory diagram showing another example of a method of manufacturing a sensor chip according to the present invention.

Fig. 4 is a schematic cross-sectional view showing one example of a sensor chip according to the present invention.

Fig. 5 is a plan view showing one step of one example of the manufacturing method according to the present invention.

Fig. 6 is a side view showing one step of one example of the manufacturing method according to the present invention.

Fig. 7 is a side view showing one step of one example of the manufacturing method according to the present invention.

Fig. 8 is a side view showing one step of another example of the manufacturing method according to the present invention.

Fig. 9 is a plan view showing a substrate used in the manufacturing method of the present invention.

Fig. 10 is a side view showing a substrate used in the manufacturing method of the present invention.

Fig. 11 is a plan view showing one step of the manufacturing method of the present invention.

Fig. 12 is a plan view showing one step of the manufacturing method of the present invention.

Fig. 13 is a side view showing one step of the manufacturing method of the present invention.

Fig. 14 is a side view showing a biosensor according to the present invention.

Explanation of Reference Signs and Symbols

1, 1', 21: Substrate board

2, 22: electrode

3, 3', 3", 23: pressure sensitive adhesive material

4, 4': spacer parts

24: Anticorrosion member (spacer member)

5, 5', 25: Groove

6, 26: Reagent (agent)

7, 27: Hollow reaction part

9, 29: Center plane

28: polyline

101: Substrate board

102: substrate

103: Overlay

104: spacer parts

105, 151, 152: Pressure-sensitive adhesive materials

105': UV curable resin

106: spacer layer

107, 107': electrodes

108: Reagent

109: Hollow reaction part

109': Groove

110: polyline

201: substrate

202, 202': electrodes

203: polyline

204: sheet layer

205, 205': Groove

206, 206': reagents

207: Pressure-sensitive adhesive materials

208: spacer layer

209: Hollow reaction part

210: line

Detailed ways

The best mode for carrying out the invention will now be described with reference to the accompanying drawings. It should be noted that the present invention is not limited to this mode, but can be modified to adopt another mode as long as the mode does not deviate from the subject matter of the present invention.

FIG. 1 shows a sensor chip and its manufacturing method according to one mode of the present invention. FIG. 1( a ) is a plan view showing a state in which electrodes 2 (detection portions) are formed on a substrate plate 1 . In this example, the electrode 2 is formed with two electrodes and corresponds to the working electrode and the counter electrode, respectively. FIG. 1( b ) is a side view showing a state in which electrodes 2 are formed on a substrate plate 1 . In this example, the electrodes 2 are formed of carbon ink and formed by screen printing on the substrate plate 1 made of PET. It should be noted that broken lines in Fig. 1(a) indicate positions corresponding to spacer members to be bonded later. Therefore, the two dotted lines on the right indicate the positions corresponding to the grooves, that is, the positions corresponding to the hollow reaction portion to be formed thereafter.

Subsequently, a pressure-sensitive adhesive material 3 as a rubber pressure-sensitive adhesive material was applied to the substrate plate 1 and the electrodes 2 by screen printing, and a spacer member 4 made of PET was bonded from above. Thus, a laminate A as shown in Fig. 1(c) was obtained. The spacer member 4 has a groove 5 , and the electrode 2 is contained in the groove 5 . Furthermore, in this example a reagent 6 is applied to the electrode 2 in the groove 5 . The plies of the laminate A are formed of a pressure-sensitive adhesive material 3 and a spacer 4 .

On the other hand, on the base plate 1' made of the same material as the base plate 1 and having the same thickness as the base plate 1, the pressure-sensitive adhesive material 3' having the same composition as the pressure-sensitive adhesive material 3 is used so that Same thickness as pressure sensitive adhesive material 3. Additionally, a spacer 4' is bonded, and a laminate B as shown in FIG. 1(d) is obtained, wherein the spacer 4' includes a groove 5' and is made of the same material as the spacer 4 and It is as thick as it is. The plies of the laminate B include a pressure-sensitive adhesive material 3' and a spacer member 4'. A laminated body can be formed by applying a pressure-sensitive adhesive material and bonding a spacer member to a single substrate plate, and by separating the obtained laminated body into two substantially equal parts, and the obtained laminated body can be Consider laminates A and B above.

The laminates A and B obtained in this way were laminated by bonding the spacer members 4 and 4' with a pressure-sensitive adhesive material 3" and obtained the sensor chip of the present invention as shown in Fig. 1 e. Pressing The sensitive adhesive material 3" is formed on the spacer 4 or the spacer 4' by screen printing. This sensor chip comprises: a substrate formed by a substrate plate 1; a cover layer formed by a substrate plate 1'; The spacer layer, and has a symmetrical structure that is symmetrical with respect to the central plane 9 as the axis. Therefore, no warpage occurs due to the lapse of time, etc. In this sensor chip, a hollow reaction part is formed by aligning the grooves 5 and 5' 7. A sample is introduced into this part, a reaction is induced and the reaction is detected by the electrode 2, after which a detection signal is output from the electrode 2 to the outside.

FIG. 2 shows another mode of the sensor chip and its manufacturing method according to the present invention. FIG. 2( a ) is a plan view showing a state in which electrodes 22 (detection portions) are formed on a substrate sheet 21 made of PET. In this example, the electrodes 22 are formed on only one side of the fold line 28 that divides the substrate plate 21 into two substantially equal parts. Also, in the above example, the electrode 22 is formed of carbon ink, and is formed by screen printing on the substrate plate 21 made of PET. In addition, the electrode 22 is formed with two electrodes and corresponds to a working electrode and a counter electrode, respectively. Dotted lines in FIG. 2( a ) indicate positions corresponding to resist members (spacer members) formed by application and curing. FIG. 2( b ) is a side view showing a state in which the electrodes 22 are formed on the substrate plate 21 .

Subsequently, on the substrate plate 21 and the electrode 22, a resist member 24 made of a thermosetting epoxy resin was applied by screen printing, which was then cured, and a laminated body as shown in FIG. 2(c) was obtained. Application and curing of the resist 24 is performed on both sides of the fold line 28 as shown in FIG. 2( c ). The resist member 24 has a pair of grooves 25 at positions symmetrical with respect to the fold line 28 as an axis, and the electrode 22 is contained in the groove 25 placed on the left side of the fold line 28 . In this example, reagent 26 is also applied to electrode 22 in recess 25 . A pair of grooves 25 in this example are formed parallel to each other and linearly.

Next, a pressure sensitive adhesive material 23, which is an acrylic solvent pressure sensitive adhesive, may be applied on at least one side of the fold line 28 on the resist member 24 by screen printing. Thereafter, the substrate sheet 21 is folded along two parallel straight lines 28' at equal distances from the fold lines 28, and a part of the resist member 24 is bonded by the pressure sensitive adhesive material 23. Therefore, the sensor chip of the present invention shown in FIG. 2( d ) can be obtained, which has a spacer layer formed of a resist member 24 and a pressure-sensitive adhesive material 23 for sealing a part of the resist The part 24 is glued to the inside of the substrate panel 21 which has been folded to form a U-shaped cross-section. A pair of grooves 25 are aligned, and a hollow reaction portion 27 is formed. Since the sensor chip has a symmetrical structure with respect to the center plane 29 as an axis, warpage does not occur due to the passage of time. Furthermore, according to the manufacturing method, the resist member 24 is applied to one layer on one substrate sheet 21, the pressure-sensitive adhesive material 23 is applied only on one side thereof, and the substrate sheet 21 is folded for bonding. Knot. Therefore, the spacer layer can be formed through only one process, and the conditions requiring the same material and the same thickness can be easily satisfied. Therefore, by using this method, the desired chip can be manufactured extremely economically and precisely.

By using the substrate plate having a length corresponding to the long side in the plan view of FIG. 1(a) or FIG. The above process of the entire surface of the plate and thereafter cutting the substrate plate along the short sides, so that a pair of electrodes can be respectively included. Multiple sensor chips can then be fabricated through a series of fabrication steps. Here, a pair of electrodes is a pair of electrodes capable of constituting one sensor chip, and includes at least two electrodes, ie, a working electrode and a counter electrode.

Furthermore, the sensor chip of the present invention can be manufactured by folding one substrate sheet and then cutting the ridges of the folded substrate sheet. FIG. 3 shows another mode of the sensor chip of the present invention. Fig. 3(a) is a side view showing a state in which the substrate sheet has been folded. The substrate sheet 31 is folded, that is, formed of a lower substrate sheet (substrate) 31a, an upper substrate sheet (cover) 31b, and a ridge 31c of the folded portion, and has a substantially U-shaped cross section. Two electrodes (detection portions) 32a, 32b are formed on the lower substrate plate 31a, and a lower long space 33a and a lower short space 33b are bonded to the electrodes 32a, 32b by a pressure-sensitive adhesive material 34. A groove 35 is formed between the lower long space 33a and the lower short space 33b, and within the groove 35 a reagent 36 can be applied to the electrodes 32a, 32b. On the upper substrate plate 31b, a pressure sensitive adhesive material 37 may be applied in positions corresponding to the lower two compartments (spacers) 33a, 33b, and bond the upper long compartment 38a and short compartment 38b. A groove 39 is formed between the upper two spacers (spacers) 38a, 38b, and the hollow reaction portion 40 is formed by the upper and lower two grooves 39, 35. The upper long space 38a and the lower short space 38b are bonded face-to-face with the lower long space 33a and the lower short space 33b by the pressure-sensitive adhesive material 41 . The method shown in FIG. 2 can be employed as an example of a manufacturing method by folding a single substrate sheet. In addition, according to this mode, each spacer formed by one layer is bonded; however, a plurality of spacers may be laminated, and in this case, it is preferable to use multiple layers for the upper spacer and the lower spacer Laminated so as to obtain equal thickness.

Sequentially, the ridges 31c are removed by cutting. First, as shown in FIG. 3( a), the movable cutting blade 42 moves along the lamination direction at a position between the portion near the upper short space 33b and the lower short space 38b to be laminated and the spine 31c. . Then, the cutting blade 40 moves from the upper substrate plate 31b toward the lower substrate plate 31a, and, as shown in FIG. Invented sensor chip 30. Typically, there is residual stress at the ridges acting in the direction where the upper and lower substrate sheets are separated since the individual substrate sheets have been folded. In the present invention, since the ridge is cut away, the step of removing the residual stress of the ridge can be eliminated, and the sensor chip can be easily manufactured.

According to the sensor chip of the present invention, residual stress can also be removed by heating the ridge of a substrate plate that has been folded. As shown in FIG. 2(a)-(d) or FIG. 3, after the substrate sheet 31 is folded, the ridge portion 31c is heated with a heating means such as a hot plate. By using such a heating device, residual stress can be removed (or reduced). Residual stress can be removed without adversely affecting the reagents while controlling the heating temperature and the heat application period (short time) to the spine.

Fig. 4 is a schematic cross-sectional view showing one example of a sensor chip according to the present invention. The sensor chip in this example has a spacer layer 106 sandwiched between a substrate 102 and a cover layer 103 . The spacer layer 106 is formed by laminating two spacer members 104 with a pressure-sensitive adhesive material 105, and has a hollow reaction portion 109 formed on one end thereof. Spacer layer 106 is bonded to substrate 102 and cover layer 103 by UV curable resin 105' adhesive.

The substrate 102 and the cover layer 103 are formed from a single substrate plate 101 . The substrate sheet 101 is folded into a U-shape along a fold line 110 used to divide the substrate sheet 101 into two substantially equal parts, one side of the fold line 110 becomes the substrate sheet 102 and the other side becomes the cover layer 103 . Therefore, as shown in FIG. 4 , the substrate 102 and the cover layer 103 are connected at one end closer to the hollow reaction portion 109 and integrally formed. An electrode 107 (detection portion) is formed on the substrate plate 101 and exposed inside a hollow reaction portion 109 in which a reagent 108 is applied to the electrode 107 .

FIG. 5 is a plan view showing a state in which many counter electrodes 107 , 107 ′ (detection sections) are formed on the substrate plate 101 . In this example, a pair of electrodes 107, 107' is formed by two electrodes corresponding to a working electrode and a counter electrode. FIG. 6 is a side view showing a state in which electrodes 107 are formed on the substrate plate 101 . In this example, the electrodes 107 are formed of carbon ink and formed by screen printing on the substrate plate 101 made of PET. In addition, as shown in FIGS. 5 and 6 , in this example, the electrode 107 is formed on the substrate 102 only on one side of the fold line 110 , and is not formed on the capping layer 103 .

An example of the manufacturing method according to the present invention will now be described. In FIG. 7(a), the laminate in which the electrodes 107 are formed on the substrate plate 101 shown in FIGS. The straight line 110 ′ is parallel to the fold line 110 and placed at an equal distance from the fold line 110 . The substrate plate 101 is made of PET, and thermoforming thereof is performed at a temperature of 160°C to 250°C. After that, in order to remove residual stress, the folded portion is heated at the same temperature. For this thermal process, the ridge folded into a U shape is brought into contact with a hot plate and held there for 1 to 2 seconds.

On the other hand, the two spacer members having the grooves are bonded using the pressure-sensitive adhesive material 105, and thereby a spacer layer having the grooves 109 as shown in FIG. 7(d) is obtained. UV curable resin 105' is applied to both sides of the spacer, and the spacer is inserted into a U-shaped molded body as shown in FIG. 7(a). For its smooth insertion, the gap between the substrate plate 101 and the cover layer 103 is widened and then closed by the inherent flexibility of PET, and after bonding, the UV curing agent 105' is cured and bonded by UV radiation. After that, a reagent is introduced into the hollow reaction portion 109, and a sensor chip as shown in FIG. 4 is obtained.

FIG. 8 is an exemplary diagram showing a step of another manufacturing method according to the present invention. In this example, two spacer members 104 are laminated with pressure sensitive adhesive material 151 , 152 on one side of the fold line 110 before the substrate panel 101 is folded. This lamination can also be performed by screen printing. In this case, the spacer elements are applied directly to the substrate plate and cured, and the pressure sensitive adhesive material is only used for the uppermost layer.

Since the spacer member 104 has a groove, and the groove 109' serving as the hollow reaction portion 109 is formed by lamination. Reagent 108 is applied to electrode 107 exposed inside recess 109'. Also, UV curable resin 105' is applied to the topmost spacer member 104, and then, at normal temperature, the base plate 101 made of PET is folded into a U shape along two straight lines 110', wherein the two straight lines 110 ′ is parallel to the fold line 110 and located at an equal distance from the fold line 110 . A thermal process for the folds is then carried out in order to remove residual stresses.

After the substrate sheet had been folded at normal temperature, while maintaining the folded state, a thermal process was performed by bringing the folded ridge into contact with a hot plate having a surface temperature of 200° C. and maintaining the state for 1 second. The use of a hot plate is useful from the standpoint of productivity and prevention of adverse reactions caused by heat, and requires a short heat application cycle. It is preferable to apply the reagent 108 at a position separated by 5 mm or more from the portion where it is in contact with the hot plate. As long as the reagents 108 are separated by 5 mm or more, the temperature of the portion to which the reagent 108 has been applied does not rise to 60° C. or higher when the thermal process is performed under the above conditions. In the case where the reagent 108 is a low heat-resistant enzyme, deterioration of the enzyme by heat does not occur.

The substrate sheet 101 and the spacer member 104 are bonded by folding the substrate sheet 101 into a U shape. Then, bonding is performed by curing the UV curable resin 105' onto the spacer member 104 with UV radiation, and the sensor chip of the present invention is obtained.

It should be noted that, in the above examples, rubber pressure-sensitive adhesive materials, acrylic pressure-sensitive adhesive materials, silicon pressure-sensitive adhesive materials, etc. may be used as the pressure-sensitive adhesive materials 105 , 151 , 152 . PET or the like can be used as the spacer member 104 . Urethane resin, epoxy resin, polyimide resin, acrylic resin, etc. can be used as the spacer member formed by screen printing.

The following example is an example of the manufacturing method of the present invention for manufacturing a plurality of sensor chips through a series of steps using a substrate on which pairs of electrodes (detection portions) are formed. FIG. 9 is a plan view showing a state in which pairs of electrodes (detection sections) 202, 202' are formed on a substrate 201. As shown in FIG. In this example, a pair of electrodes 202, 202' is formed of two electrodes and corresponds to a working electrode and a counter electrode, respectively. FIG. 10 is a side view showing a state in which an electrode 202 is formed on a substrate 201. As shown in FIG. In this example, the electrodes 202, 202' are formed of carbon ink and formed by screen printing on the substrate 201 made of PET resin. The electrodes can also be formed by performing a method other than screen printing such as a method of bonding a metal tape to a substrate.

The dotted lines in FIGS. 9 and 10 indicate a fold line 203 that divides the substrate 201 into two approximately equal parts and two straight lines 203', wherein the two straight lines 203' are parallel to the fold line 203 and placed at a distance from the fold line 203. equidistant positions. As shown in FIGS. 9 and 10 , the electrodes 202 , 202 ′ are formed on only one side of the fold line 203 in this example.

Layer 204 is laminated to the substrate shown in FIGS. 9 and 10 . FIG. 11 is a plan view showing a state after the sheet layers 204 are laminated. Two linear grooves 205 , 205 ′ are formed in the sheet 204 , wherein the two linear grooves 205 , 205 ′ are positioned equidistant from and parallel to the fold line 203 . The sheet 204 with the grooves 205, 205' is formed by applying resin to the substrate by screen printing. The resin applied by screen printing may be polyurethane resin, epoxy resin, denatured polyimide resin, acrylic resin, and the like.

In accordance with the method of performing resin screen printing on a substrate, it is preferable to consider productivity because sheet layers can be laminated by individual application. Furthermore, the position and shape of the grooves 205, 205' can be easily changed by simply changing the printing plate. By marking the surface of the electrode in a prescribed area so as to make the electrode area constant, the sheet 204 serves as a space for forming sensor chips and also serves to reduce detection variation of the sensor, so the sheet 204 is generally called a resist layer. Once the sheets 204 are laminated, a pressure sensitive adhesive material, adhesive, etc. can be applied by screen printing, wherein the pressure sensitive adhesive material, adhesive, has the function of being able to bond both sides when folding is performed. . A rubber pressure-sensitive adhesive material, an acrylic pressure-sensitive adhesive material, a silicon pressure-sensitive adhesive material, and the like can be used as the pressure-sensitive adhesive material applied by screen printing. In addition, epoxy adhesives, vinyl acetate adhesives, silicon adhesives, and the like can be used as the adhesive.

A coating machine, such as a dispenser with two nozzles, then applies the reagent to the grooves 205, 205'. These two nozzles correspond to the grooves 205, 205', and since the grooves 205, 205' extend along two parallel straight lines, the two nozzles only need to move in parallel, therefore, by a single process, the The reagent is applied over the entire length of both grooves. That is, according to the present invention, based on the fact that there are two surfaces on the same plane, using a coater, a reagent can be applied to both grooves in the lower surface and the upper surface by the same process. It should be noted that one nozzle can be used to apply reagents to both grooves. However, this is preferable from an economical point of view, because when two nozzles are provided in one coater for the lower surface and the upper surface, two coatings of the grooves can be performed in the same application cycle. Coating of the surface, which is the same as in the case where the reagent is applied to one surface of the groove. By using different reagent supply lines for the two nozzles, ie by supplying different reagents to separate nozzles, different reagents can be applied to the grooves 205, 205'. 12 and 13 are respectively a plan view and a side view showing a state where the reagents 206, 206' have been applied.

It should be noted that in this example the reagents 206, 206' are applied after the grooves 205, 205' have been formed. After the reagent 206, 206' has been applied, the recess 205, 205' may be formed in order to contain the reagent inside it. However, it is preferred to perform the method of reagent application after the grooves 205, 205' have been formed, since the positioning of the application and the control of the amount applied are easier.

Substrate 201 is folded along fold line 203 after the reagent has been applied. In this example, the base sheet 201 is folded along two straight lines 203' parallel to the fold line 203 and equidistant from the fold line 203, and forms a U-shaped cross-section. Fig. 14 is a side view of the folded state. Folding may be performed at normal temperature; however, preferably, after the substrate has been folded, a heat process is performed at the folded portion in order to remove residual stress.

It is generally preferable that the temperature of the thermal process using the thermoplastic resin is equal to or higher than the middle value of the resin softening temperature (glass transition temperature) and melting point, and equal to or lower than the melting point. When the heat history temperature is lower than the intermediate value between the resin softening temperature (glass transition temperature) and the melting point, the residual stress of the folded portion cannot be properly removed, and the folded portion will be changed with the lapse of time. On the other hand, when the thermal process temperature exceeds the melting point, deformation of the resin increases, and a smooth folded surface cannot be maintained. Since PET resin has a resin softening temperature of about 70°C and a melting point of about 250°C, it is preferable that the heat history temperature of the folded portion is lower than or higher than 160°C and equal to Or below 250°C. A typical PET resin may be Melinex or Tetoron (product name, manufactured by Teinin DuPont Films Japan, Ltd.), Lumirror (product name, Toray Industries Inc.), or the like.

On the other hand, since an enzyme such as GOD or GDH may deteriorate at a temperature of 60° C. or higher, it is preferable for a biosensor chip employing such an enzyme to perform adjustments such as adjusting the thermal process temperature and separating the hollow reaction portion from the broken line. Separate the process by an appropriate distance such that the set portion of the enzyme is not equal to or above 60°C.

In the case of such a mode in which the base sheet 201 is made of PET resin, the following method is employed as an exemplary preferred mode. After the substrate sheet had been folded at normal temperature, while maintaining the folded state, thermal processing was performed by bringing the folded ridge into contact with a hot plate with a surface temperature of 200° C. and by maintaining the state for one second. Using a hot plate is useful from the viewpoint of productivity and prevention of adverse effects caused by heat because localized heating can be easily performed and a short heat application period is required. Preferably, the reagent 108 is applied at a position 5 mm or more away from the portion in contact with the hot plate. As long as the reagents 108 were separated by 5 mm or more, the temperature on the portion to which the reagent 6 had been applied did not rise to 60° C. or higher when the thermal process was performed under the above conditions. In the case where Reagent 6 is a low heat-resistant enzyme, deterioration of the enzyme by heat does not occur.

After folding, the folded substrate panel 204 is bonded by a pressure sensitive adhesive material 207 to form a spacer layer 208 . As described above, a rubber pressure-sensitive adhesive material, an acrylic pressure-sensitive adhesive material, a silicon pressure-sensitive adhesive material, or the like can be used as the pressure-sensitive adhesive material 207 . The grooves 205, 205' can also be aligned to form a hollow reaction portion 209, and reagents 206, 206' can be applied to the lower and upper surfaces. After cutting the laminate thus obtained along a straight line (straight line 210 shown in FIG. 9 ) perpendicular to the fold line 203 , a plurality of individual sensor chips having a side view shown in FIG. 14 can be obtained. The load-cut process is performed such that at least one pair of electrodes is included in each sensor chip.

Claims (25)

1. A sensor chip, comprising: Substrate; cover layer; a spacer layer sandwiched between the substrate and the cover layer; a hollow reaction part disposed between the substrate and the capping layer; and a detection part, which is set in the hollow reaction part, wherein the substrate and cover are made of the same material and have equal thickness, and The material and shape of the spacer layer are symmetrical about a plane parallel to the substrate and equidistant from the substrate and cap layer. 2. The sensor chip according to claim 1, wherein the spacer layer is formed by bonding together a pair of sheets having grooves and made of a single-layer or multi-layer spacer, each pair of sheets is made of the same material and is of equal thickness, and Pairs of plies are bonded together so as to be symmetrical about the plane. 3. The sensor chip as claimed in claim 2, wherein after the laminate is formed by laminating the sheets on the substrate plates serving as the base and the cover, the sheets have symmetry with respect to a broken line serving as an axis. a pair of grooves, a fold line dividing the substrate plate into two substantially equal parts, whereby at least one of the grooves contains a detection portion therein, folding the laminate over along the fold lines so that a pair of grooves are aligned with each other so as to form a hollow reactive portion, and bonding the parts of the sheet together, Thus, a sensor chip was obtained. 4. The sensor chip of claim 3, wherein the pair of grooves are parallel to each other and linearly shaped. 5. The sensor chip according to any one of claims 1 to 4, wherein the sensor chip is a biosensor chip. 6. A method of manufacturing a sensor chip having a substrate, a cover layer, a spacer layer sandwiched between the substrate and the cover layer, a hollow reaction part provided between the substrate and the cover layer, and a A detection section within a hollow reaction section, the method comprising: forming a detection portion on a substrate plate serving as a substrate or a cover layer; and The laminate (1) and the laminate (2) are bonded so that the sheets of the two laminates (1) and the laminate (2) face each other, and the sheets of the two sheets are The grooves are aligned with each other, thereby forming a hollow reaction part, Wherein, the laminated body (1) is obtained by forming a sheet layer having a groove and made of a single-layer or multi-layer spacer, so that the detection portion is contained in the groove, and The substrate panels and plies of the laminate (2) are made of the same material and have the same thickness and configuration as those of the laminate (1). 7. A method of manufacturing a sensor chip having a substrate, a cover layer, a spacer layer interposed between the substrate and the cover layer, a hollow reaction portion provided between the substrate and the cover layer, and The detection part provided in the hollow reaction part, the method includes: forming a detection portion on a substrate plate serving as a substrate and a cover layer; A laminated body is formed by laminating sheets having a pair of grooves symmetrical about a fold line serving as an axis such that at least one of the grooves contains a detecting portion therein, the sheet being a spacer member or a plurality of a laminate of spacer members, the fold line dividing the substrate sheet into two approximately equal parts; After forming the laminate, folding the laminate along the fold lines so that the sheets face each other; and Bond the sheets together. 8. A method of manufacturing a sensor chip having a substrate, a cover layer, a spacer layer interposed between the substrate and the cover layer, a hollow reaction part provided between the substrate and the cover layer, and a device In the detection section within the hollow reaction section, the method includes: forming a detection portion on a substrate plate serving as a substrate and a cover layer; Spacer layers are respectively formed on the substrate and the cover layer, the spacer layer is a spacer or a laminated body of a plurality of spacer parts, and grooves are respectively formed in each spacer layer so that at least one of the grooves has a detection department; bonding the spacer layers together by folding up the substrate sheet, and forming a hollow reaction portion by making the grooves face each other; and The folded portion of the substrate sheet is formed after bonding the spacer layers together and forms the hollow reaction portion. 9. A method of manufacturing a sensor chip comprising a substrate, a cover layer, a spacer layer sandwiched between the substrate and the cover layer, a hollow reaction part provided between the substrate and the cover layer, and The detection part provided in the hollow reaction part, the method includes: forming a detection portion on a substrate plate serving as a substrate and a cover layer; Forming spacer layers on the substrate and the cover layer respectively, the spacer layer being a spacer member or a laminate of a plurality of spacer members, and forming grooves in the spacer layer respectively so as to have a detection portion in at least one groove; bonding the spacer layers together by folding the substrate sheets and forming the hollow reaction portion by making the grooves face each other; and After bonding the spacer layers together and forming the hollow reaction portion, the folded portion of the substrate sheet is heated. 10. A sensor chip, comprising: Substrate; cover layer; a spacer layer sandwiched between the substrate and the cover layer; a hollow reaction part disposed between the substrate and the capping layer; and a detection part, which is set in the hollow reaction part, Wherein, the substrate and the cover layer are connected to each other at one end of the substrate and one end of the cover layer, and are integrally formed. 11. The sensor chip of claim 10, wherein the substrate and cover are formed by folding a substrate sheet along a fold line dividing the substrate sheet into two substantially equal parts. 12. The sensor chip according to claim 10 or 11, wherein the sensor chip is a biosensor chip. 13. A method of manufacturing a sensor chip having a substrate, a cover layer, a spacer layer interposed between the substrate and the cover layer, a hollow reaction portion provided between the substrate and the cover layer, and The detection part provided in the hollow reaction part, the method includes: A detection portion is formed on at least one side of a substrate sheet and a fold line that divides the substrate sheet into two substantially equal parts; Fold the substrate sheet along the fold line; inserting a spacer layer having grooved portions between the folded substrate panels; and A spacer layer is bonded to the folded substrate sheet in order to obtain a laminate. 14. A method of manufacturing a sensor chip having a substrate, a cover layer, a spacer layer sandwiched between the substrate and the cover layer, a hollow reaction part provided between the substrate and the cover layer, and a device In the detection section within the hollow reaction section, the method includes: A detection portion and a spacer layer having a groove portion are formed on at least one side of a substrate plate and a fold line that divides the substrate plate into two substantially equal parts; folding the substrate sheet along the fold line; and The spacer layer and the other side of the substrate sheet are bonded to obtain a laminate. 15. The method of manufacturing a sensor chip according to claim 13 or 14, wherein the substrate is made of thermoplastic resin, and After the substrate sheet is folded, a thermal process is applied on the folded portion. 16. The method for manufacturing a sensor chip according to any one of claims 13 to 15, further comprising: forming a plurality of pairs of detection parts, while arranging the detection parts in a direction parallel to the broken line; and The obtained laminate is cut along one or more straight lines perpendicular to the fold lines, so that at least one pair of detection portions is included in each sensor chip. 17. A method of manufacturing a sensor chip having folded substrates, a spacer layer sandwiched between the folded substrates, a hollow reaction part provided between the folded substrates, and a hollow reaction part provided in the hollow reaction part The detection part, the method includes: The laminated body (1) is obtained by laminating a sheet layer having a pair or more than one pair of grooves symmetrical about a fold line as an axis, which separates the substrate divided into two substantially equal parts, whereby at least one groove contains the detection portion; simultaneously applying reagents to the substrate at locations corresponding to individual wells of the pair of wells; and After these two steps, the laminate (1) is folded along the fold lines and the parts of the plies are glued together to form the spacer layer. 18. The method of manufacturing a sensor chip as claimed in claim 17, wherein the lamination of the sheet layer having multiple layers symmetrical with respect to the broken line used as the axis is performed in one step by applying the resin to the substrate. in a pair of grooves. 19. The method of manufacturing a sensor chip according to claim 17 or 18, wherein the laminate (1) is obtained by forming a sheet with paired grooves after application of the reagent. 20. The method of manufacturing a sensor chip according to claim 17 or 18, wherein the reagent is applied after the laminate (1) is obtained by forming a sheet with paired grooves. 21. The method of manufacturing a sensor chip according to any one of claims 17 to 20, wherein the grooves of the groove pair are parallel and linearly shaped. 22. The method of manufacturing a sensor chip according to any one of claims 17 to 21, wherein different reagents are simultaneously applied to positions corresponding to respective grooves of the pair of grooves. 23. The method of manufacturing a sensor chip according to any one of claims 17 to 22, wherein the detection part formed on the substrate includes a plurality of pairs of detection parts arranged in a direction parallel to the fold line, and The manufacturing method also includes: The formed laminate (2) is cut along one or more straight lines perpendicular to the fold lines so that at least one pair of detection portions is included in each sensor chip. 24. A sensor chip manufactured according to the manufacturing method according to any one of claims 17 to 23. 25. The sensor chip of claim 24, wherein the sensor chip is a biosensor chip.

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